Saturday 13 July 2002 21.47 EDT
First published on Saturday 13 July 2002 21.47 EDT

Valerie Brown always assumed she knew what she was going to do when she hit her menopause: she was going to take hormone replacement therapy. She was going to sail into old age feeling young and staying healthy; she was not going to be a victim of her hormones.

But last Wednesday morning Brown, a landscape gardener in her late forties, was searching the internet for alternatives after shrill headlines revealed that the biggest study ever conducted into HRT had been abruptly halted amid unexpected findings that, far from protecting women, the so-called wonder drug was doing more harm than good.

The news that the long-awaited US-based study had been abandoned three years early after women exhibited an increase in breast cancer cases, strokes and blood clots sparked concern across the world: the Australian government issued a plea for calm while the British Government ordered an urgent investigation into the study.

The research was the conversation of the week for countless women, thousands of whom flooded their doctors' clinics with unscheduled visits and phone calls. Some were angry but most were just afraid. 'Now I don't know what to do,' Brown said.

Her concern was echoed by billions of women around the world - six million HRT prescriptions were issued in England alone last year - but, as the week wore on and the dust settled, it became clear this weekend that the dilemma facing women was far less agonising than many had feared.

The research is 'just another brick in the wall of what we already knew', said Dr David Ontjes, a co-investigator on the study, based at the University of North Carolina. 'This simply confirms what we have suspected for some time, which is that it is all right to take HRT for four to five years when the symptoms of the menopause are most severe, but beyond that most women should probably not take any form of HRT that we know of today.'

The researchers found that women should no longer consider combination hormone therapy to protect themselves from osteoporosis or other chronic diseases, or to achieve a general sense of wellbeing.

Equally, however, women should not panic or stop taking the treatment without consulting their doctor, say scientists, medical staff and other experts. Not only is the risk for individuals very small, but the information confirmed by the study is discussed in detail in the leaflets that are contained alongside each HRT treatment.

The headlines that caused the upset announced that the risk of developing breast cancer was increased by 26 per cent for women who took the American HRT-compound Prempro for more than five years, while the risk of having a heart attack or other coronary event was up by 29 per cent and strokes by 41 per cent. But although it was published in the highly respected Journal of the American Medical Association (JAMA), leaders of the US government-funded Women's Health Initiative have moved to distance themselves from the way in which the research was presented.

'Announcing statistics in percentages like these was perhaps not the best idea,' conceded Ontjes, who is determined that the results should not be taken out of context. 'There's no terrible danger and no cause for panic. These are small statistical differences, even for heart disease, and we have to interpret them cautiously.'

A 26 per cent rise in breast cancer may sound alarming, he said, but in real terms it means a difference of less than one case in each 1,000 women per year; a 29 per cent rise in heart attack or other coronary events affects seven women out of every 10,000. Total mortality between the two groups was indistinguishable.

Their recommendation, however, only applied to women taking oestrogen and progesterone and not to women in a separate study evaluating the use of oestrogen alone.

Women who have had a hysterectomy are often prescribed oestrogen only, a treatment whose risks and benefits are also uncertain. Because they had not detected any significant increase in breast cancer in that group, researchers confirmed that study would continue.

'This is the major trial of HRT the world has been waiting for,' Britain's foremost expert in HRT, Professor Valerie Beral, said. Beral is conducting the UK's biggest study into the issue and maintains that, although the specific drug used in the study is not available in Britain, the findings hold firm across the board. 'There's virtually no evidence to suggest that different types of oestrogen and progestogen [a synthetic version of progesterone] have different effects,' she said. 'This answers all the questions about HRT we have ever asked.'

The British Government has asked the Committee for Safety of Medicines to report on the study, but Professor Alasdair Breckenridge, chairman of the committee, insisted that the results simply give increased credence to the practice already followed by the British medical profession: that, although it is useful for the average woman to take HRT for a few years to relieve their menstrual symptoms, there is no good evidence that the overall effects of oestrogen make it worth taking for 10 to 20 years.

'HRT has never been licensed in Britain for anything except the alleviation of short-term relief of menopausal symptoms,' he said. 'These findings are relevant to someone taking HRT for relatively trivial reasons, and not to anyone taking it because they are at great risk of osteoporosis.'

The study was not abandoned because of a realisation that those taking part were at risk, he emphasised, but because it simply achieved its purpose five years earlier than expected - which was to establish whether oestrogen plus progesterone has a favourable or unfavourable effect on heart disease incidence and on overall risks and benefits in predominantly healthy women.

'The reason this study was stopped was not because of any one event, but because it had became clear that researchers would not see any benefits in long-term use,' said Dr Victoria Kusiak, managing director, vice-president of global medical affairs and North American director of Wyeth, Prempro's maker. 'There was, quite simply, no point in continuing.'

Ontjes agreed. 'The proportion of risk to benefit was high enough after five years that, even if we had continued the study as planned, there would not have been a U-turn: the benefit of taking HRT in the long term does not outweigh the risks for most women,' he said.

The risk to an individual woman is so small, however, that Ontjes admitted that if a user felt strongly that her quality of life was considerably enhanced by continuing to take the combined treatment, he would support her choice.

'I would not push a woman hard to stop taking HRT after whatever period of time if she was going well and had no history or other reason to develop breast cancer,' he said. 'The quality of life of an individual woman may be worth the small risk of these complications. This is why it has to be a personal decision for each woman, based on a conversation with her GP.'

Catherine Landes, an accountant in her mid-fifties, has already made her decision. 'I'm continuing with HRT,' she said. 'I was a late convert to the treatment, and experienced the full horror of boiling hot flushes that left me soaking wet from head to toe, two to three times an hour, day and night, for a whole year until I started taking HRT.

'I had palpitations, was permanently dizzy and felt sick most of the time,' she added. 'The flushes stopped me sleeping and my mood changes swung dangerously close to depression.'

That the treatment made Landes feel better is indisputable, but experts have warned that many women suffering far less severe symptoms may be unwilling to give up HRT because they are mistakenly attributing almost magical powers of rejuvenation to it.

'HRT has been shown to relieve problems of menopause, and there's no question that women using it feel a lot better,' Beral said. 'But there is an idea that has pervaded a lot of clinics that not only do you feel better on HRT but your health is improved too.'

No study into HRT has ever found evidence that the drug affects the users' general health. In every investigation, women on both HRT and a placebo drug reported exactly the same increased levels of wellbeing. 'An increase in overall health has never has been proven,' added Beral. 'It is, as far as I am concerned, a myth entirely without foundation.'

Alongside a scrupulously healthy lifestyle, there are many alternative methods for women to relieve both the short and long-term effects of the menopause, including natural hormones; low doses of anti-depressant drugs, such as Prozac; and Clonidine, a drug prescribed for high blood pressure. Soy-rich foods may also help, as does vitamin E.

'The bottom line is that oestrogen is still going to be given in the short term to relieve menopausal symptoms,' Ontjes said. 'This study simply gives physicians more information on which to base their reluctance to prescribe it for long-term use.' The benefits

The benefits are indisputable and were confirmed in this study:

· A 37 per cent reduction in bowel cancer.

· A 33 per cent reduction in hip fracture.

· A 24 per cent reduction in all fractures.

Add to this emerging evidence that HRT can probably prevent Alzheimer's and is 98 per cent effective in treating menopausal symptoms such as hot flushes, night sweats and dry vagina. It also keeps women's genital organs healthy, including the bladder, and therefore protects against cystitis.